title: LC, LC-MS/TOF and MS(n) studies for the identification and characterization of degradation products of nelfinavir mesylate.
abstract: The objective of the present investigation was to separate, identify and characterize the major degradation products (DPs) of nelfinavir mesylate generated under hydrolytic, oxidative, photolytic and thermal stress conditions as advised in International Conference on Harmonization (ICH) guideline Q1A(R2). The drug was found to degrade under acidic, basic, oxidative and photolytic stress, while it was stable in neutral and thermal stress conditions. A total of three degradation products were formed, which were separated on a C-18 column employing a gradient HPLC method. A complete mass fragmentation pathway of the drug was first established with the help of multi-stage (MS(n)) and MS/TOF accurate mass studies. Then stressed samples were subjected to LC-MS/TOF studies, which provided their fragmentation pattern and accurate masses. The mass spectral data were employed to characterize the DPs and assign structures to them. The total information was also used to establish the degradation pathway of the drug. The degradation products were identified as 3-hydroxy-N-((2R,3R)-3-hydroxy-1-(phenylthio)butan-2-yl)-2-methylbenzamide and (3S,4aS,8aS)-N-tert-butyl-2-((2R,3R)-2-hydroxy-3-(3-hydroxy-2-methylbenzamido)-4-(phenylsulfinyl)butyl)decahydroisoquinoline-3-carboxamide.
authors.affiliation: Department of Pharmaceutical Chemistry, SVKM's NMIMS, School of Pharmacy and Technology Management, Near Bank of Tapi River, Agra-Mumbai Road Babulde, Shirpur Dist., Dhule 425405, Maharashtra, India. ravisun4@rediffmail.com
authors.forename: Ravi N
authors.initials: RN
authors.lastname: Tiwari
authors.forename: Chandrakant G
authors.initials: CG
authors.lastname: Bonde
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D004355:Drug Stability; D017408:Guidelines as Topic; D017320:HIV Protease Inhibitors / Q000032:analysis* / Q000737:chemistry; D006868:Hydrolysis; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D008956:Models, Chemical; D015394:Molecular Structure; D019888:Nelfinavir / Q000032:analysis* / Q000737:chemistry; D010084:Oxidation-Reduction; D010782:Photolysis; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D013696:Temperature
chemical_list: D017320:HIV Protease Inhibitors; D019888:Nelfinavir